Mediating function of heart failure in the causal relationship between diastolic blood pressure and hypertensive renal disease with renal failure:a mediated Mendelian randomization study

Objective:To study the causality relationship between diastolic blood pressure(DBP)and hypertensive renal disease with renal failure(HRDRF)and the mediating role of hear t failure(HF)in the causality relationship by network Mendelian randomization(MR).Methods:Genome-wide analysis of DBP,HRDRF,and HF was downloaded from the public database(Genome-Wide Analysis Study[GWAS])and was used to analyze the results and to conduct mediated MR analysis.Results:Analysis showed that DBP was positively correlated with HRDRF(OR=1.0002,95%CI:1.0001–1.0003,P=1.8076e-05)and DBP was positively correlated with HF(OR=1.0295,95%CI:1.0221–1.0370,P=2.5292e-15).HF and HRDRF had a positive causal effect(OR=1.0001,95%CI:1.0000–1.0001,P=0.0152).Mediation analysis showed that the contribution ratio of HF to the combined effect of DBP and HRDRF was 24.69%.Conclusions:DBP can increase the risk of renal disease with renal failure,and HF may play an impor tant role in mediating this causal relationship.

Blood-brain barrier pathology in cerebral small vessel disease

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

The Effect of Blood Lipid Profiles on Chronic Kidney Disease in a Prospective Cohort:Based on a Regression Discontinuity Design

Objective Previous studies on the association between lipid profiles and chronic kidney disease(CKD)have yielded inconsistent results and no defined thresholds for blood lipids.Methods A prospective cohort study including 32,351 subjects who completed baseline and follow-up surveys over 5 years was conducted.Restricted cubic splines and Cox models were used to examine the association between the lipid profiles and CKD.A regression discontinuity design was used to determine the cutoff value of lipid profiles that was significantly associated with increased the risk of CKD.Results Over a median follow-up time of 2.2(0.5,4.2)years,648(2.00%)subjects developed CKD.The lipid profiles that were significantly and linearly related to CKD included total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),TC/HDL-C,and TG/HDL-C,whereas lowdensity lipoprotein cholesterol(LDL-C)and LDL-C/HDL-C were nonlinearly correlated with CKD.TC,TG,TC/HDL-C,and TG/HDL-C showed an upward jump at the cutoff value,increasing the risk of CKD by 0.90%,1.50%,2.30%,and 1.60%,respectively,whereas HDL-C showed a downward jump at the cutoff value,reducing this risk by 1.0%.Female and participants with dyslipidemia had a higher risk of CKD,while the cutoff values for the different characteristics of the population were different.Conclusion There was a significant association between lipid profiles and CKD in a prospective cohort from Northwest China,while TG,TC/HDL-C,and TG/HDL-C showed a stronger risk association.The specific cutoff values of lipid profiles may provide a clinical reference for screening or diagnosing CKD risk.

Blood cell counts and nonalcoholic fatty liver disease: Evidence from Mendelian randomization analysis

BACKGROUND Previous research has highlighted correlations between blood cell counts and chronic liver disease.Nonetheless,the causal relationships remain unknown.AIM To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease(NAFLD)risk.METHODS Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study(GWAS)conducted by the Blood Cell Consortium.Summary-level data for liver enzymes were obtained from the United Kingdom Biobank.NAFLD data were obtained from a GWAS meta-analysis(8434 cases and 770180 controls,discovery dataset)and the Fingen GWAS(2275 cases and 372727 controls,replication dataset).This analysis was conducted using the inverse-variance weighted method,followed by various sensitivity analyses.RESULTS One SD increase in the genetically predicted haemoglobin concentration(HGB)was associated with aβof 0.0078(95%CI:0.0059-0.0096),0.0108(95%CI:0.0080-0.0136),0.0361(95%CI:0.0156-0.0567),and 0.0083(95%CI:00046-0.0121)for alkaline phosphatase(ALP),alanine aminotransferase(ALT),aspartate aminotransferase,and gammaglutamyl transferase,respectively.Genetically predicted haematocrit was associated with ALP(β=0.0078,95%CI:0.0052-0.0104)and ALT(β=0.0057,95%CI:0.0039-0.0075).Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD[odds ratio(OR)=1.199,95%CI:1.087-1.322]and(OR=1.157,95%CI:1.071-1.250).The results of the sensitivity analyses remained significant.CONCLUSION Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis,which may facilitate the diagnosis and prevention of NAFLD.

Lowering of Blood Lipid Levels with a Combination of Pitavastatin and Ezetimibe in Patients with Coronary Heart Disease:A Meta-Analysis

Objectives:According to the findings of randomized controlled trials,blood lipid levels in patients with coronary heart disease(CHD)can be significantly decreased through a combination of pitavastatin and ezetimibe;however,the effects and clinical applications of this treatment remain controversial.This meta-analysis was aimed at objectively assessing the efficacy and safety of pitavastatin and ezetimibe in lowering blood lipid levels.Design:Relevant studies were retrieved from electronic databases,including PubMed,Cochrane Library,Embase,China National Knowledge Infrastructure,VIP,and WanFang Data,from database inception to June 8,2022.The lev-els of low-density lipoprotein cholesterol,total cholesterol,triglycerides,and high-density lipoprotein cholesterol in patients’serum after treatment were the primary endpoint.Results:Nine randomized controlled trials(2586 patients)met the inclusion criteria.The meta-analysis indi-cated that pitavastatin plus ezetimibe resulted in significantly lower levels of LDL-C[standardized mean difference(SMD)=−0.86,95%confidence interval(CI)(−1.15 to−0.58),P<0.01],TC[SMD=−0.84,95%CI(−1.10 to−0.59),P<0.01],and TG[SMD=−0.59,95%CI(−0.89 to−0.28),P<0.01]than pitavastatin alone.Conclusions:Pitavastatin plus ezetimibe significantly decreased serum LDL-C,TC,and TG levels in patients with CHD.

Analysis of Blood Lipids, Blood Glucose, Blood Uric Acid, and Blood Routine Test Results in Retired Employees of a Unit in the Civil Aviation System

Objective:To investigate and analyze the annual physical examination results of retired employees from a unit in the civil aviation system,focusing on blood lipids,blood glucose,blood uric acid,and blood routine results.The study aims to provide relevant references for formulating reasonable disease management measures for preventing and controlling hyperlipidemia,hyperuricemia,and other conditions in retired employees.Methods:The examination results of 231 participants were collected and analyzed.The participants were divided into four groups based on age:middle-aged group,young-old group,middle-old group,and old-old group.The blood test results were compared across these groups,and an assessment of atherosclerotic cardiovascular disease(ASCVD)risk levels was completed in conjunction with medical history.Blood test results were also compared by gender.Results:There were no significant statistical differences in blood test results when grouped by age.However,the prevalence of hyperuricemia was higher in males than in females,while the prevalence of hypercholesterolemia was higher in females than in males.The LDL-C target achievement rate was lower in the moderate-and-high-risk group as well as the very high-risk group as defined by ASCVD risk levels.Conclusion:Management of hyperuricemia and hyperlipidemia in retired employees(elderly patients)should be strengthened to reduce the risk of ASCVD events and alleviate the potential medical burden associated with disease progression.

Comparative Analysis of Budesonide Treatments on Blood Gas and Inflammation in Chronic Obstructive Pulmonary Disease Remission

Objective:To investigate the effects of budesonide on blood gas and inflammation indexes in patients with chronic obstructive pulmonary disease(COPD)during remission.Methods:Fifty-one patients with COPD in remission,admitted to Zhongshan Hospital of Dalian University from July 2021 to December 2022,were selected and divided into two groups based on a randomized numerical table method.The control group(25 cases)received budesonide formoterol treatment,while the observation group(26 cases)received budesonide geforce treatment.Various indexes,including clinical efficacy,blood gas indexes,inflammation indexes,St.George’s Respiratory Questionnaire(SGRQ)scores,Chronic Obstructive Pulmonary Disease Assessment Test(CAT)scores,and 6-minute Walking Distance Test(6MWD)results,were compared between the two groups.Results:After 21 days of treatment,the total clinical effectiveness rate of the observation group was higher than that of the control group,with a statistically significant difference(P<0.05).Post-treatment,the PaO2 level and pH value in both groups were higher,and the PaCO_(2) level was lower compared to pre-treatment levels.The observation group showed better improvements in these indicators than the control group,with statistically significant differences(P<0.05).SGRQ and CAT scores for both groups were lower post-treatment,with the observation group scoring lower than the control group.Additionally,the 6MWD results were farther for both groups post-treatment,with the observation group achieving greater distances than the control group,with statistically significant differences(P<0.05).Conclusion:Budesonide can effectively improve blood gas indexes in patients with COPD in remission,alleviate related clinical symptoms,reduce inflammatory responses,and promote patient recovery.The treatment efficacy is significant.

Most patients with non-hypertensive diseases at a critical care resuscitation unit require arterial pressure monitoring: a prospective observational study

BACKGROUND:Blood pressure(BP)monitoring is essential for patient care.Invasive arterial BP(IABP)is more accurate than non-invasive BP(NIBP),although the clinical signifi cance of this diff erence is unknown.We hypothesized that IABP would result in a change of management(COM)among patients with non-hypertensive diseases in the acute phase of resuscitation.METHODS:This prospective study included adults admitted to the Critical Care Resuscitation Unit(CCRU)with non-hypertensive disease from February 1,2019,to May 31,2021.Management plans to maintain a mean arterial pressure>65 mmHg(1 mmHg=0.133 kPa)were recorded in real time for both NIBP and IABP measurements.A COM was defined as a discrepancy between IABP and NIBP that resulted in an increase/decrease or addition/discontinuation of a medication/infusion.Classification and regression tree analysis identified significant variables associated with a COM and assigned relative variable importance(RVI)values.RESULTS:Among the 206 patients analyzed,a COM occurred in 94(45.6%[94/206])patients.The most common COM was an increase in current infusion dosages(40 patients,19.4%).Patients receiving norepinephrine at arterial cannulation were more likely to have a COM compared with those without(45[47.9%]vs.32[28.6%],P=0.004).Receiving norepinephrine(relative variable importance[RVI]100%)was the most signifi cant factor associated with a COM.No complications were identifi ed with IABP use.CONCLUSION:A COM occurred in 94(45.6%)non-hypertensive patients in the CCRU.Receiving vasopressors was the greatest factor associated with COM.Clinicians should consider IABP monitoring more often in non-hypertensive patients requiring norepinephrine in the acute resuscitation phase.Further studies are necessary to confi rm the risk-to-benefi t ratios of IABP among these high-risk patients.

Effects of Combined Inhalation of Budesonide,Formoterol,and Tiotropium Bromide on Arterial Blood Gas and Pulmonary Function Indexes in Patients with Chronic Obstructive Pulmonary Disease

Objective:To analyze the effect of combined inhalation of budesonide formoterol and tiotropium bromide on arterial blood gas and pulmonary function indexes in patients with chronic obstructive pulmonary disease(COPD).Methods:100 patients with COPD treated from January to December 2022 were selected as observation objects,and were divided into a control group(n=50,in which budesonide and formoterol were administered)and an experimental group(n=50,the treatment drug was budesonide formoterol combined with tiotropium bromide)according to the computer grouping method,and compared the treatment results.Results:(i)Before treatment,there was no difference in the partial pressure of carbon dioxide and partial pressure of oxygen between the control group and the experimental group(P>0.05);after treatment,the partial pressure of carbon dioxide and partial pressure of oxygen in the experimental group were higher than those in the control group,with significant differences(P<0.05).(ii)Before treatment,there was no difference in forced vital capacity(FVC),forced expiratory volume in one second(FEV1),FEV1/FVC between the control group and the experimental group(P>0.05);after treatment,the FVC,FEV1,and FEV1/FVC in the experimental group were significantly higher than those in the control group(P<0.05).(iii)There was no difference in the levels of CRP,IL-6,and TNF-αbetween the control group and the experimental group(P>0.05);after treatment,the levels of CRP,IL-6,and TNF-αin the experimental group were lower than those in the control group,with significant differences(P<0.05).(iv)Compared to the total incidence of adverse reactions in the control group(28.00%),the incidence of total adverse reactions in the experimental group was lower at 10.00%,and the difference was significant(P<0.05).Conclusion:The combined inhalation of budesonide and formoterol with tiotropium bromide has demonstrated a clear therapeutic efficacy and safety in treating chronic obstructive pulmonary disease.This treatment approach effectively enhances arterial blood gas levels and lung function,showing promising potential for widespread application.

TREATMENT OF ACUTE DISEASES OF PHARYNX AND LARYNX WITH BLOOD-PRICKING THERAPY

This article deals with a treatment of acute diseases of pharynx and larynx with bloodpricking therapy, in this treatment, a group of 79 patients accepted the treatment with this therapy.The therapy contains mainly two methods: Acupoint pricking and local scattered pricking. A good result is achieved. It proves that blood-pricking method can replace the antibiotics and alleviate the sufferer’s pain and economic burden. It is simple and easy to carry out, thus it can be spread extensively.

Effects of low molecular weight heparin on the function of blood coagulation and serum levels of TNF-α, CK-MB, CRP of patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failur

Objective:To study the effects of low molecular weight heparin on the function of blood coagulation and serum levels of tumor necrosis factor-α(TNF-α), creatine kinase isoenzyme (CK-MB), C-reactive protein (CRP) of patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failure.Methods:A total of 80 patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failure in our hospital from June 2014 to October 2016 were enrolled in this study. The subjects were divided into the control group (n=40) and the treatment group (n=40) randomly. The control group were treated with conventional treatment, the treatment group were treated with the conventional treatment combined with low molecular weight heparin. The two groups were treated for 7 d. The D-dimer (D-D), fibrinogen (FBG), pro thrombin time (PT), thrombin time (TT), TNF-α, CK-MB and CRP of the two groups before and after treatment were compared.Results:There were no significantly differences of the blood levels of D-D, FBG, PT and TT of the two groups before treatment. After treatment, the blood levels of D-D and FBG of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group, the PT and TT of the two groups were significantly higher than before treatment, and that of the treatment group were significantly higher than the control group. There were no significantly differences of the serum levels of the TNF-α, CK-MB and CRP of the two groups before treatment. After treatment, the serum levels of the TNF-α, CK-MB and CRP of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group.Conclusion:Low molecular weight heparin can significantly reduce the inflammatory factors of the patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failure, can alleviath the patients conditions and reduce the myocardial damage.

Evaluating the causal relationship between human blood metabolites and gastroesophageal reflux disease

BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes.As a powerful statistical tool,Mendelian randomization(MR)is widely used to explore the causal relationship between exposure and outcome.AIM To analyze of the relationship between 486 blood metabolites and GERD.METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD.A genome-wide association study(GWAS)of 486 metabolites was the exposure,and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis.Bonferroni correction is used to determine causal correlation features(P<1.03×10^(-4)).The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy.Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD.In addition,metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.RESULTS In MR analysis,four blood metabolites are negatively correlated with GERD:Levulinate(4-oxovalerate),stearate(18:0),adrenate(22:4n6)and p-acetamidophenylglucuronide.However,we also found a positive correlation between four blood metabolites and GERD:Kynurenine,1-linoleoylglycerophosphoethanolamine,butyrylcarnitine and guanosine.And bonferroni correction showed that butyrylcarnitine(odd ratio 1.10,95% confidence interval:1.05-1.16,P=7.71×10^(-5))was the most reliable causal metabolite.In addition,one significant pathways,the"glycerophospholipid metabolism"pathway,can be involved in the pathogenesis of GERD.CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD,which will help further elucidate the pathogenesis of GERD and better guide its treatment.At the same time,this also contributes to early screening and prevention of GERD.However,the results of this study require further confirmation from both basic and clinical real-world studies.

Retrospective analysis of perianal Paget's disease with underlying anorectal carcinoma

AIM:To analyze clinical and pathological characteristics of an aggressive subtype of perianal Paget's disease(PPD) and explore its rational treatment modalities.METHODS:PPD patients were retrospectively collected in the institutional colorectal database of the Fudan University Shanghai Cancer Center.Detailed patient histories of past medical condition,diagnosis,treatment,and pathological findings were reviewed.Surgical specimen from diagnosis and surgery were reviewed by two independent pathologists for confirmation of diagnoses.Follow up was accomplished by clinical interview by cellphone.RESULTS:In total,eight cases of PPD were analyzed.All patients had underlying anorectal adenocarcinoma,including seven with synchronous lesions and one with metachronous lesions.Moreover,all anorectal lesions had a mucin-producing component.The median age at diagnosis was 65(range 29-81 years),and the male/female ratio was 7:1.The Median follow-up time of all patients was 61.5 mo(range 10-204 mo).One patient treated with abdominoperineal resection(APR) died from lung metastases 10 mo after the APR operation.The other patients are still free of disease at the time of this analysis.CONCLUSION:PPD is a rare malignancy and is easily misdiagnosed.Underlying anorectal cancer was not unusual and was a significant prognostic factor.Rational treatment of both anorectal cancer and PPD lesion is essential for long-term survival.

Differences in the predictive value of red cell distribution width for the mortality of patients with heart failure due to various heart diseases

Background Increased red blood cell distribution width （RDW） is associated with adverse outcomes in patients with heart failure （HF）. The objective of this study was to compare the differences in the predictive value of RDW in patients with HF due to different causes. Methods We retrospectively investigated 1,021 HF patients from October 2009 to December 2011 at Fuwai Hospital （Beijing, China）. HF in these patients was caused by three diseases; coronary heart disease （CHD）, dilated cardiomyopathy （DCM） and valvular heart disease （VHD）. Patients were followed-up for 21 ~ 9 months. Results The RDW, mortality and survival duration were significantly different among the three groups. Kaplan-Meier analysis showed that the cumulative survival decreased significantly with increased RDW in patients with HF caused by CHD and DCM, but not in those with HF patients caused by VHD. In a multivariable model, RDW was identified as an independent predictor for the mortality of HF patients with CHD （P 〈 0.001, HR 1.315, 95% CI 1.122-1.543）. The group with higher N-terminal pro-brain natriuretic peptide （NT-proBNP） and higher RDW than median had the lowest cumulative survival in patients with HF due to CHD, but not in patients with HF due to DCM. Conclusions RDW is a prognostic indicator for patients with HF caused by CHD and DCM; thus, RDW adds important information to NT-proBNP in CHD caused HF patients.

Association of ABO blood groups with the severity of coronary artery disease: a cross-sectional study

Objective To investigate whether ABO blood groups is associated with the severity of coronary artery disease(CAD). Methods Between January 2015 and December 2017, 1425 first diagnosed CAD patients confirmed by selective coronary angiography were recruited into this cross-sectional study, and their baseline characteristics, ABO blood groups, Gensini score were collected. Multiple linear regression analysis was performed to test the association between the severity of CAD and ABO blood groups. Results The Gensini score was significantly higher in the blood group A than in the non-A groups(41.2 ± 32 vs. 38 ± 27;P = 0.026). After adjusting for age, male, smoking, family history of CAD, hypertension, diabetes mellitus and hypercholesterolemia, multivariate linear regression indicated that blood group A was associated with the severity of CAD(β= 3.298, 95% CI: 0.91–6.505, P = 0.044). In diabetes group, A blood type was also associated with increased Gensini score(P = 0.02) after adjusting for age, male, family history of CAD, hypercholesterolemia, smoking and hypertension. Conclusion In this cross-sectional study, the data indicated that blood group A was an independent risk factor of severity of CAD in Chinese population and Chinese patients with type 2 diabetes.

Red blood cell distribution width in elderly hospitalized patients with cardiovascular disease

BACKGROUND Red blood cell distribution width(RDW)is elevated in patients with cardiovascular disease(CVD).AIM To determine RDW values and impact of CV and non-CV coexisting morbidities in elderly patients hospitalized with chronic CVD.METHODS This prospective study included 204 consecutive elderly patients(age 77.5[7.41]years,female 94[46%],left ventricular ejection fraction 53.00%[37.50,55.00])hospitalized with chronic CVD at the Cardiology Department of Larissa University General Hospital(Larissa,Greece)from January 2019 to April 2019.Elderly patients were selected due to the high prevalence of coexisting morbidities in this patient population.Hospitalized patients with acute CVD(acute coronary syndromes,new-onset heart failure[HF],and acute pericarditis/myocarditis),primary isolated valvular heart disease,sepsis,and those with a history of blood transfusions or cancer were excluded.The evaluation of the patients within 24 h from admission included clinical examination,laboratory blood tests,and echocardiography.RESULTS The most common cardiac morbidities were hypertension and coronary artery disease,with acutely decompensated chronic heart failure(ADCHF)and atrial fibrillation(AF)also frequently being present.The most common non-cardiac morbidities were anemia and chronic kidney disease followed by diabetes mellitus,chronic obstructive pulmonary disease,and sleep apnea.RDW was significantly elevated 15.48(2.15);121(59.3%)of patients had RDW>14.5%which represents the upper limit of normal in our institution.Factors associated with RDW in stepwise regression analysis were ADCHF(coefficient:1.406;95%confidence interval[CI]:0.830-1.981;P<0.001),AF(1.192;0.673 to 1.711;P<0.001),and anemia(0.806;0.256 to 1.355;P=0.004).ADCHF was the most significant factor associated with RDW.RDW was on average 1.41 higher for patients with than without ADCHF,1.19 higher for patients with than without AF,and 0.81 higher for patients with than without anemia.When patients were grouped based on the presence or absence of anemia,ADCHF and AF,heart rate was not increased in those with anemia but was significantly increased in those with ADCHF or AF.CONCLUSION RDW was elevated in elderly hospitalized patients with chronic CVD.Factors associated with RDW were anemia and CV factors associated with elevated heart rate(ADCHF,AF),suggesting sympathetic overactivity.

TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS:A total of 391 serum samples were examined in this study.Samples were obtained from healthy blood donors(n=110),hepatitis B surface antigen(HBsAg)-positive donors(n=112),anti-hepatitis C virus(anti-HCV)-positive donors(n=69),patients with type B chronic liver disease (n=81),and patients with type C chronic liver disease(n=19). Trv DNA was detected using the hemi-nested PCR.HGV RNA was tested using RT-PCR.A history of blood transfusion and serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were also determined. RESULTS:TTV DNA was detected in 8.2%of healthy blood donors,16.1%of HBsAg-positive donors,20.3%of anti- HCV-positive donors,21.0%of patients with type B chronic liver disease,and 21.1%of patients with type C chronic liver disease.HGV RNA was detected in 1.8%of healthy blood donors,1.8%of HBsAg-positive donors,17.4%of anti-HCV-positive donors,13.6%of patients with type B chronic liver disease,and 10.5%of patients with type C chronic liver disease.The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors(P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors.There was a history of transfusion in 66.7%of TTV DNA-positive patients and 76.9%of HGV RNA-positive patients(P<0.05).No significant increase in serum ALT and AST was detected in the TTV or HGV-positive donors and patients. CONCLUSION:TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors.However,there is no significant association between TTV or HGV infections and liver injury.

Emerging blood exosome-based biomarkers for preclinical and clinical Alzheimer's disease:a meta-analysis and systematic review

Blood exosomes,which are extracellular vesicles secreted by living cells into the circulating blood,are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease states.An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer's disease.Therefo re,we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer's disease,mild cognitive impairment,and Alzheimer's disease.We performed a literature search in PubMed,Web of Science,Embase,and Cochrane Library from their inception to August 15,2020.The research subjects mainly included Alzheimer's disease,mild cognitive impairment,and preclinical Alzheimer's disease.We identified 34 observational studies,of which 15 were included in the quantitative analysis(Newcastle-Ottawa Scale score 5.87 points)and 19 were used in the qualitative analysis.The meta-analysis results showed that core biomarkers including Aβ_(1-42),P-T181-tau,P-S396-tau,and T-tau were increased in blood neuro nderived exosomes of preclinical Alzheimer's disease,mild cognitive impairment,and Alzheimer's disease patients.M olecules related to additional risk facto rs that are involved in neuroinflammation(C1q),metabolism disorder(P-S312-IRS-1),neurotrophic deficiency(HGF),vascular injury(VEGF-D),and autophagy-lysosomal system dysfunction(cathepsin D)were also increased.At the gene level,the differential expression of transc ription-related factors(REST)and microRNAs(miR-132)also affects RNA splicing,transport,and translation.These pathological changes contribute to neural loss and synaptic dysfunction.The data confirm that the above-mentioned core molecules and additional ris k-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer's disease.These findings support further development of exosome biomarkers for a clinical blood test for Alzheimer's disease.This meta-analysis was registered at the International Prospective Register of Systematic Reviews(Registration No.CRD4200173498,28/04/2020).

Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases

Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a f ixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient' s tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a "one-by-one" administration schedule. Evidencebased clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within wellconstructed protocols will offer better prospects for blood conservation in selected IBD patients undergoing elective surgery.

Bacteremia in Subjects with Sickle Cell Disease: High Rate of Gram-Negative Isolates in the West African Context!

Background: Sickle cell disease is one of the most common monogenic diseases in the world, affecting approximately 70 million people, 80% in sub-Saharan Africa and 1 in 10 in Senegal. Sickle cell anemia causes functional asplenia (associated with repeated thrombosis of splenic vessels), resulting in increased susceptibility to infection. However, several studies have reported differences in the spectrum of bacterial infections in malaria-endemic areas. Therefore, we proposed to conduct a study to determine the rate of positive blood cultures and the bacteriological spectrum in sickle cell patients. Materials and Method: This is a descriptive cross-sectional study of blood culture samples from patients who received a request for hemoglobin electrophoresis as part of their treatment at the Principal’s hospital in Dakar. The study took place from January 2008 to December 2021. For each patient, we collect demographic information, including age, gender, and the service from which the analysis request originated. Data were collected in the laboratory’s computer system and entered into Microsoft Excel (2007). Statistical analyzes were performed using Epi-Info 7 software. Results: Our study included 1419 patients. The most common types of hemoglobin profiles were: normal profile (n = 1025), AS profile (n = 283), SS profile (n = 104), SC profile (n = 7). This corresponds to the proportions of 72%, 20%, 0.5% and 7.5% for the profiles Normal, AS, SC and SS. The male proportion was 61.1%, 61.5%, 57.1, respectively %, 55.8% for Normal, SA, SC, and SS profiles. A total of 19,090 individual blood culture bottles were collected from 1419 impatient patients as follows: Normal profile (n = 18,042 bottles), AS profile (n = 677 culture bottles), SS profile (n = 362 bottles). The majority of blood culture orders come from pediatric services, accounting for 70% of the total number of orders. Of 19,090 vials examined in this current study, 19.6% developed a positive blood culture. Overall, the most commonly isolated bacteria were Staphylococci (41.1%), Enterobacteriaceae (36.7%), Bacillaceae (10.2%), unfermented (6.30%), Streptococci (5.01%), and a small proportion of yeast (0.75%). There is no significant difference in bacterial spectrum between the SS profile and the normal profile of individuals (p = 0.104). Coagulase-negative staphylococci accounted for 32%, 24%, and 40% of the species isolated in the normal AS and SS profiles. respectively. Coagulase-negative staphylococci were the most commonly isolated organisms in SS. Group E and sptagged streptococci each account for less than 2% of the organisms isolated in SS. Pneumococci were not found. Bacillus accounts for 25% of isolates in SS subjects compared to 9% in normal and AS subjects, respectively. Pseudomonas aeruginosa and Burkholderia cepacia then make up 10% of the isolates in the subjects of the SS profile as non-fermenters. Conclusion: Our study shows that enterobacteria and staph are prevalent in people with sickle cell disease. There is no significant difference in bacterial spectrum between SS subjects compared to subjects with a normal profile. The rarity of Streptococcus pneumoniae in bacteremia isolates underlines the need for further studies with larger patient numbers to better understand the spectrum of bacterial infections in patients with sickle cell disease in West Africa.